Abstract

A flurry of recent revelations is challenging the current dogma on how ubiquitin-dependent processes culminate in the activation of NF-kappa B, by TNF. Here, we integrate these findings into a model for TNF-R1 signaling-and underscore the importance of individual components, including linear ubiquitin chains-which allows for the remarkable versatility of the ubiquitin system.

We would like to apologise to all scientists who contributed to the field of TNF-R signaling and whose work could not be cited due to space restrictions. We would like to thank David Barford for providing the Ub structures, and members of the Meier lab for discussions and help with preparation of this manuscript. We acknowledge support from Cancer Research UK and NHS funding to the NIHR Biomedical Research Centre.